title: Novel medium-term carcinogenesis model for lung squamous cell carcinoma induced by N-nitroso-tris-chloroethylurea in mice.
abstract: Targeted treatments for lung cancer based on pathological diagnoses are required to enhance therapeutic efficacy. There are few well-established animal models for lung squamous cell carcinoma although several highly reproducible mouse models for lung adenoma and adenocarcinoma are available. This study was carried out to establish a new lung squamous cell carcinoma mouse model. In the first experiment, female A/J mice were painted topically on back skin twice weekly with 75 μL 0.013 M N-nitroso-tris-chloroethylurea for 2, 4, and 8 weeks (n = 15-20 per group) as initiation of lung lesions, and surviving mice were killed at 18 weeks. In the second experiment, mice were treated as above for 4 weeks and killed at 6, 12, or 18 weeks (n = 3 per group). Lung lobes were subjected to histopathological, immunohistochemical, immunoblotting, and ultrastructural analyses. In the case of treatment for 2, 4, and 8 weeks, incidences of lung squamous cell carcinoma were 25, 54, and 71%, respectively. Cytokeratin 5/6 and epidermal growth factor receptor were clearly expressed in dysplasia and squamous cell carcinoma. Desmosomes and tonofilaments developed in the squamous cell carcinoma. Considering the carcinogenesis model, we conclude that 2 or 4 weeks of N-nitroso-tris-chloroethylurea treatment may be suitable for investigating new chemicals for promotional or suppressive effects on lung squamous cell carcinoma.
authors.affiliation: Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tago
authors.forename: Shotaro
authors.initials: S
authors.lastname: Yamano
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Kitano
authors.forename: Masaki
authors.initials: M
authors.lastname: Fujioka
authors.forename: Naomi
authors.initials: N
authors.lastname: Ishii
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000139:chemically induced*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D002330:Carmustine / Q000031:analogs & derivatives* / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate
chemical_list: C572573:N-nitroso-tris-chloroethylurea; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C460223:Cyp2a4 protein, mouse; C101679:Cyp2b10 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D000072467:Cytochrome P450 Family 2; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D002330:Carmustine